Recent Updates on Indole Derivatives as Kinase Inhibitors in the Treatment of Cancer.

Cancer is becoming a global threat as its treatment accounts for many challenges. Hence, newer inventions prioritize the requirement of developing novel anticancer agents. In this context, kinases have been exclusively investigated and developed as a promising and novel class of drug targets for anticancer regimen. Indole derivatives have been found to be most effective for targeting multiple kinases, such as PIM, CDK, TK, AKT, SRC, PI3K, PKD, GSK, etc., to inhibit cell proliferation for cancer. Recently, a group of researchers have proposed their research outcomes related to this moiety, such as Zhang et al. described some potent PI3K inhibitors by substitution at the 4th position of the indole ring. Kassis et al. enumerated several potent CDK5 inhibitors by substituting the 2nd and 6th positions of the indole ring. In the present review, we have taken the initiative to summarize structure-activity relationship (SAR) studies of indole derivatives as kinase inhibitors for the development of potential inhibitors.

The Recent Development of Piperazine and Piperidine Derivatives as Antipsychotic Agents.

Schizophrenia is a chronic neuropsychiatric disorder that affects nearly 1% of the global population. There are various anti-psychotic drugs available for the treatment of schizophrenia, but they have certain side effects; therefore, there is a need to explore and develop novel potential lead compounds against schizophrenia. The currently available drugs e.g. typical and atypical antipsychotics act on different dopamine and serotonin receptors and as per literature reports, various piperidine and piperazine derivatives have shown promising activity against these receptors. When different heterocyclic groups are attached to basic piperidine and piperazine rings, the antipsychotic activity is greatly potentiated. In this direction, various antipsychotic drugs have been synthesized at the laboratory level, and few are under clinical trial studies, such as Lu AE58054, PF-04802540, ORG25935, DMXB-A, Bitopertin, and ABT-126. In the present review, we include the studies related to the effect of different substituents on piperidine/piperazine derivatives and their anti-psychotic activity. Various series of synthesized compounds by other researchers with piperidine/piperazine nucleus have been reviewed and diagrammatically represented in the form of SAR (structure-activity relationships), which will help the scientists for the development of potential lead compounds.

Current Insights into the Chemistry and Antitubercular Potential of Benzimidazole and Imidazole Derivatives.

Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives have been found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure-activity relationships in the treatment of tuberculosis.

An exhaustive perspective on structural insights of SGLT2 inhibitors: A novel class of antidiabetic agent.

Diabetes mellitus is the global health issue and become an alarming threat in the modern era where human lifestyle gets compromised with modernization. According to the latest statistical report 2020, USA has 9.47% (31 million among 32.72 cr), China has 8.3% (116.4 million among 139.27 cr) and India has 5.6% (77 million among 135.26 cr) of the diabetic people, indicating that diabetes is more prevailing in developed countries as compared to the developing countries. The number of diabetic patients is rising day by day at a tremendous rate and soon it may affect each and every person in a family. So, there is an urgent need to develop novel entities that can meet the scarcity of present antidiabetic agents. In the last few decades, the sodium-glucose co-transporter 2 (SGLT2) has emerged as a prominent target for the treatment of Type 2 diabetes mellitus due to its novel mechanism of action & no involvement in insulin signaling pathway. Most of the inhibitors that target SGLT2 contain three basic moieties: glucose, two benzene rings (one is connected with glucose and the other with methylene), and the methylene bridge which are similar to dapagliflozin. Several SGLT2 inhibitors and their derivatives such as remogliflozin etabonate (phase-II), sotagliflozin (phase-III) and bexagliflozin (phase-III) are under different phases of clinical trial studies and some have been patented. The present review is focused on SGLT2 inhibitors, structure activity relationships (SARs) of dapagliflozin and its several analogues for their binding affinity with SGLT2. We have also presented and summarized the efforts made by various researchers in terms of the synthesis of various dapagliflozin derivatives till date.

Central nervous system fungal infection--a report of three cases.

Fungal infections of the central nervous system in three apparently immunocompetent patients are being reported. Two cases of cerebral aspergillosis presenting as intracranial granulomas such as rhinocerebral and intracranial forms, and one of cryptococcal meningitis could be successfully diagnosed by newer diagnostic modality such as antigen detection techniques. The case with cryptococcal infection had typical neuroimaging feature which helped to suspect the underlying diagnosis. Aspergillus galactomannan detection in the cerebrospinal fluid helped in the early diagnosis and appropriate therapy of one patient.

Epidemiological study of neurological disorders in a rural population of Eastern India.

The study was conducted to determine the prevalence of neurological diseases in a rural community in Eastern India through a community based survey with the help of trained doctors following on WHO protocol (1981) translated in local vernacular, among 20842 rural residents (male-11037, female-9805, census India-1991, the State of West Bengal in Eastern India) over a period of one yearfrom May 1992 to April 1993 in two phases. Professionals screened the patients by house to house survey in the first phase and later on they were examined in details in temporary clinics in second phase. A total of 606 patients were identified and classified according to well-defined diagnostic criteria. The commonest diseases per 100,000 were headache: 870, vertebral diseases with neurological involvement: 540, seizure disorders: 360, vertigo: 230, stroke: 147, movement disorders: 140, peripheral neuropathy: 80. The age and sex specific prevalence showed increasing frequency of neurological disorders with advancing age in both genders excepting slight dip in the fourth and fifth decades among females. In the present study prevalence of headache, epilepsy, stroke and Parkinson's disease was lower than that of in the Western countries. Different inclusion criteria, multiethnicity, different environmental factors, poor medical facility and insufficient number of aged population may be responsible for lower prevalence of chronic neurological disorders as compared to Western countries. Increase in the life expectancy in future will lead to increasing burden of chronic neurological diseases in absolute term in Indian society considering the one billion population at present.